Four children with familial hyperlysinemia have been investigated in this laboratory. From results thus obtained and from information reported elsewhere, it can be shown that a deficiency of lysine:ketoglutarate reductase activity in these patients prevents them from converting lysine to saccharopine. Similarly an alternate path of lysine catabolism by way of formation of pipecolic acid has been demonstrated for them. Evidence has been gathered indicating that hypusine is derived from lysine in these patients. Further studies are designed to: (1) Continue serial clinical and biochemical studies on the 3 surviving children with familial hyperlysinemia in order to monitor the natural history of this condition, (2) Complete measurements of levels of free amino acids (especially lysine and lysine metabolites) in tissues of one patient who died, (3) Complete gross and microscopic pathologic studies for this patient, (4) Assess the capacity of young infants and children to handle oral loads of lysine in order to evaluate the various paths available to them for lysine metabolism, (5) Look for evidence to support the presence in hyperlysinemics of a "lysine urea cycle".